NL8005187A - CYTOSTATICALLY ACTING PHARMACEUTICAL PREPARATIONS, NEW ISOCYANIC ACID DERIVATIVES AND METHODS FOR PREPARING THEM. - Google Patents

Description

• € N.O. 29,399

Cytostatically acting pharmaceutical preparations, new isocyanuric acid derivatives and processes for their preparation

It is known that a series of Allied products unfold a cytostatic or cytotoxic action. The best known compounds are derived from the so-called nitrogen discharge. In addition, it is also known to use at least two epox3 / groups in the molecule containing compounds as cancerostatics. Such compounds are, for example, 4,4'-bis - (- - epoxypropyl-di-piperidinyl-Cl. the 1.2-15.16-deepoxy-4.7-10.13-te-traoxohexadecane. Certainly the last compounds 10 have not brought any significant improvement in the cytostatic treatment and are hardly used. They are only occasionally used for the treatment of brain tumors. The limited solubility of the listed compounds also prevents wider use.

The subject of the unpublished German Offenlegungsschrift 2,907,3 ^ -9 are drug preparations with cytostatic activity, which contain as pharmacologically active substance triglycidyl isocyanurate (IGI) and / or such BGI derivatives, in which the hydrogen of the carbon-20 atom in the 2-position of the glycidyl group can be replaced by an alkyl radical with 1 to 4 carbon atoms. Compounds of this type are distinguished in that the three nitrogen atoms of the isocyanuric acid ring are substituted with glycidyl radicals containing epoxy groups, which may also be substituted in the 2-position by an alkyl radical with 1 to 4 carbon atoms.

The present invention is based on the finding that structure-analogous compounds which, however, contain only two glycidyl-30 groups on the isocyanuric acid ring in H-substitution and substituents selected on the other IT atom, also unfold a surprisingly strong cytostatic activity. can even surpass the efficacy of TGI.

Accordingly, subject of the present invention are, in a first embodiment, drug preparations with cytostatic activity containing compounds of the general formula 1, wherein R is the following beta-n * 1 δ 7

cL

knowledge may include: alkyl, aryl, aralkyl, alkaryl, cycloalkyl, which radicals may optionally also be of a heterocyclic nature, unsaturated and / or substituted with at least one of the following substituents: halogen, hydroxy, 5 amino, IT -substituted amino, mercapto, alkyl mercapto, aryl mercapto, alkyl sulfoxy, aryl sulfoxy, alkoxy, aroxy, acyloxy and a heterocyclic moiety. The glycidyl radical corresponds to the general formula 2, wherein in this formula R 2 is preferably hydrogen, but it can also represent an alkyl group 10 with 1 to 4 carbon atoms.

As substituted radicals R in the compounds of the general formula 1, the suitably substituted alkyl radicals are preferred. As unsaturated residues, ethylenically unsaturated residues, in particular corresponding to monounsaturated residues, are preferred.

The invention furthermore encompasses the novel compounds characterized according to formula, as well as processes for their preparation. -

The mechanism of action of the compounds used in the context of the invention has not been elucidated in detail. The glycidyl groups also present here, as in the triglycidyl isocyanurate of German Offenlegungsschrift 2.9C7.J4-9, are presumably of significance for the cytostatic action. All of the compounds of the general formula I according to the invention described are characterized by the presence of two such glycidyl groups. In addition, the rest R, which can be varied widely, is present in the respective connection class. It is possible that via this residue R an influence is exerted on the distribution of lipophilic and hydrophilic preferences and that the absorption of the compounds can thereby be controlled to some extent by the organism. However, the significance of the new substituent R introduced according to the invention should not be limited thereto.

The radical R according to the above definition is a hydrocarbon radical, which may also contain heteroatoms. IT, 0, S and / or P are particularly suitable as heteroatoms. Preferably, each of these radicals contains no more than 15 carbon atoms in total, preferably no more than 4-0 than 12 carbon atoms, and expediently no more than 8005187

A X

X

J

8 carbon atoms. Interestingly, residues containing up to 6 or preferably even up to only 4 carbon atoms can be particularly interesting, these numerical values being conceivable independently of the structure in question and 5 relating only to the sum of all carbon atoms in the residue concerned.

When R represents an aryl, aralkyl or alkaryl radical, 1-core substituents are particularly preferred here. Typical representatives are phenyl, benzyl, tolyl, xylyl and related compounds. Also preferred in the cycloaliphatic rings for the radical R is mononuclear ring systems based on cyclopentyl, cyclohexyl and derivatives thereof. Corresponding heterocyclic radicals, in particular also mononuclear ring compounds with 0, 1 and / or S in the system, are within the scope of the invention. Ring systems may preferably contain 1, 2 or 3 of such heteroatoms. These heterocyclic radicals preferably contain 5 or 6 ring atoms. In addition, all of the annular substituents mentioned herein, whether of an aromatic or cycloaliphatic nature, may in turn contain further substituents. Suitable substituents are, for example, halogen, hydroxy or alkoxy.

In a particularly preferred embodiment of the invention, the radical R represents an optionally substituted alkyl radical. This alkyl moiety may be straight or branched and saturated or unsaturated and, with the exclusion of its substituents, preferably contains no more than 10, in particular no less than 8, carbon atoms. Particularly preferred in this embodiment of the invention are those compounds of the general formula 1 wherein the radical R represents unsubstituted alkyl of 1 to 6 carbon atoms or a corresponding alkyl radical, those of halogen, hydroxy, amino, N -substituted amino, mercapto, alkyimercapto, arylmer-capto, alkylsulfoxy, arylsulfoxy, alkoxy, aroxy and / or acyloxy is substituted, the substituent also being of a heterocyclic nature.

In addition, such substituted radicals may be substituted once or several times with said groups.

Preferably, 1 to 3 of the said substituents are present in ft η n 5 1 r 7 τ- the corresponding radical R, with, in a particularly preferred case, such substituted alkyl radicals of the above-mentioned type containing compounds having the general formula 1 are used in the pharmaceutical preparations according to the invention.

Are substituted groups present in the substituted alkyl radical R, which in turn contain hydrocarbon radicals - in particular in the case of the radicals N-substituted amino, alkyl mercapto, aryl mercapto, alkyl-10 sulfoxy, aryl sulfoxy, alkoxy, aroxy and acyloxy - then these substituent groups preferably contain no more than 10, advantageously no less than 8 carbon atoms. The particularly preferred limit here is 6 carbon atoms, in particular no more than 4 carbon-15 atoms. These substituting hydrocarbon radicals may in turn be aryl, aralkyl, alkaryl, cycloalkyl and / or alkyl radicals, which may also optionally contain substituents such as halogen, hydroxy, alkoxy and the like. Also included here are heteroatoms containing radicals of the type outlined above, so for example heterocyclic ring systems with 1 to 3 heteroatoms of the type outlined above - in particular mononuclear rings with N, 0 and / or S as heteroatoms. Preferred are the corresponding 5- or 6-membered heterocyclic rings.

In an especially preferred embodiment, compounds of the general formula I are used, wherein the radical R represents a mono- or disubstituted alkyl radical of the said type selected from the following groups: monohydroxyalkyl dihydroxy-30 alkyl, halohydroxyalkyl, N-substituted aminohydroxyalkyl, alkyl mercaptohydroxyalkyl, substituted alkylmer captohydroxyalkyl, the corresponding alkylsulfoxyhydroxyalkyl radicals, optionally substituted alkoxyhydroxyalkyl and optionally substituted acyloxyhydroxyalkyl. Preferably, the alkyl radicals up to 7, preferably 3 to 7, in particular 3, may be added here. Contain 4 or 5 carbon atoms.

Within the scope of the invention, compounds of the general formula I can be used in which the radical R represents straight or branched, unsubstituted alkyl with at most 40 6, preferably at most 4 carbon atoms.

80 0 5 1 8 7 5

Particularly suitable are the radicals methyl, ethyl, propyl, isopropyl as well as the corresponding C radicals and their ethereally unsaturated analogues. Torch is very particularly preferred for those compounds of general formula 1, in which the radical R is a mono- or disubstituted alkyl radical of the said type with in particular 3 carbon atoms and preferably contains at least one hydroxyl group. Here, therefore, at least one hydroxyl group - preferably next to another substituent on this residue - is always present.

According to a further preferred embodiment of the invention, these substituent groups are distributed over the 2- and 3-pools of the residue R in question. The hydroxyl group can be present either at the 2-15 position or at the 3-β-ate. Particularly preferred torch are suitably substituted compounds of the formula 1 which, in the radical R, have no other substituent in addition to the hydroxyl group or as further substituents hydroxy, halogen, a--substituted amino radical, an optionally substituted alkoxy residue, an optionally substituted alkyl mercapto radical respectively contain alkyl sulfoxy residue or an optionally substituted acylcxy residue. Chlorine and / or bromine are particularly preferred as halogen, however fluorine and cod are not excluded. The IT-substituted amino radicals correspond to the formulas 3. Here, the radicals are respectively hydrocarbon radicals, which in turn may be substituted. In the preferred embodiment of the invention, these radicals R 2 and 30 and optionally R 2 contain up to 12 carbon atoms, with the sum of the radicals R 2 and R 2 preferably not exceeding 12 carbon atoms when the nitrogen is substituted. Particularly preferably, these substituents R0 and R2 together contain at most 8 and in particular 35 not more than 5 carbon atoms. The residues Rp and R- may also be attached to a saturated or unsaturated, optionally aromatic and / or heterocyclic ring. Preferably, IO and optionally R, Cck are alkyl radicals. If these radicals are in turn substituted once again, 40 are contemplated in the context of the invention as such substituents 8005187, in particular hydroxy, alkoxy or halogen, preferably chlorine or bromine. If, in addition to the hydroxyl group, an acyloxy radical, an alkoxy radical or an alkyl-mercapto or alkyl sulfoxy radical is present in H, then this radical preferably optionally contains at most 10 carbon atoms, the preferred limit here also being 8 carbon atoms and it is particularly preferred to introduce no more than 5 carbon atoms at this location in the molecule. Preference is also given to alkyl radicals with the corresponding number of carbon atoms, which also exclude aryl radicals. The acyloxy radicals are preferably derived from monocarboxylic acids with the said carbon number and structure.

The medicaments according to the invention may preferably contain individually defined compounds of the general formula 1, however, it has been found that mixtures of active substances of several valley compounds under the formula 5T = common compounds are also highly active cytostatics. In the context of the invention, it may furthermore be preferred to use individual certain or a mixture of some compounds of the definition according to the invention according to formula 1 mixed with the 1GI compounds according to the mentioned earlier German patent application 2.907.34-9. .

The preparation of the active substances of formula 1 is a further subject of the invention. In principle, the preparation can take place in a manner known per se. The following possibilities are listed: 1. Conversion of triglycidyl isocyanurate with an excess of water, alcohol, primary and / or secondary amines, mercaptans, imines, imides, carboxylic acids, hydrogen halide and the like or hydrogen.

Due to the equivalence of the three glycidyl groups in the TGI, this reaction always leads to product mixtures, which in turn can be therapeutically effective. However, it is also possible, and part of the method of the invention outlined in the following, to separate the corresponding compounds of the general formula 1 from these mixtures by suitable separation methods, for example preparative thin-layer chromatography or colon chromatography. Within the framework of these conversions, a glycidyl group is converted to the residue E of the compounds of general formula 1. In the reductive treatment of the glycidyl group with hydrogen or hydrogen-generating compounds, a mono-hydroxyalkyl radical E is formed. As hydrogen-generating compounds, for example, hydride compounds, for example complex borohydrides such as sodium borohydride, can be used. In the other cases mentioned, the triglycidyl moiety is reacted in excess with a nucleophilic compound ΗΦΑΘ, resulting in a disubstituted residue E, which, in addition to a hydroxyl group, has the residue Αθ as the second substituent usually with respect to the hydroxylated carbon atom of the remainder contains H.

In principle, the reaction of the glycidyl groups of the 23-1 with such nucleophilic reaction partners is known in the art and described, for example,

Angew. Chemistry SC, (1968), 85 ^. This reaction is directed in the prior art to carry out more than just a few threads of the 201 and, for example, serves to cross-link epoxy resin systems on an industrial scale. In the process according to the invention, on the other hand, preferred process conditions were chosen, which allow for an increase in yield so far aimed at 1: 1 reaction products, as well as the subsequent isolation and recovery of these 1: 1 reaction products. separation of unreacted parts of the starting material and further propagation settlements resulting from the reaction of more than just one epoxy group with the nucleophilic reaction partner.

When converting IG-I compounds with nucleophilic reaction partners of the type outlined above, it may be difficult to obtain the desired 1 t 1 reactants in preferred yields, because three epoxy groups of the molecule of the starting material molecule r-40 bond are about the same in the reaction and therefore often the desired diglycidyl compound is not formed as the preferred reaction product. Also, the attempt to enrich the desired compound by reacting the triglycidyl isocyanurate with an excess of nucleophilic reaction partner has only been found to be real in few cases, because in many cases a polymerization of the triglycidyl isocyanurate occurs very easily.

The recovery of the 1: 1 reaction product is, as a rule, successful only when the mercaptans, amines and hydrides are selected as reagents. Here partial ring-opening products of the desired constitution can be obtained with starting mixtures containing the reagents in the ratio 1: 1 or in only a slight excess of one of the reagents.

It is already more difficult to recover the corresponding reaction products from the DGI with, for example, carboxylic acids, water or alcohols.

It has been found that the preparation of the Ί: 1 reaction products becomes surprisingly simple when the triglycidyl isocyanurate is reacted with an excess, preferably a large excess of the nucleophilic reagent ΗβΑθ, but the reaction is terminated prematurely and the excess of the nucleophilic reaction partner, unreacted TGI and co-formed di- and tri-addition products. The residual crude diglycidyl product can then be purified in the usual manner, for example, by column chromatography. Preferably, in this method, the nucleophilic reaction partner is used in a 3 to 30-fold excess, especially in a 5 to 20-fold excess to the required amount. The conversion can be carried out in solvents, however, if desired, the excess of the nucleophilic reaction partner can also serve as a solvent. If solvents are to be used, they should advantageously be substantially polar, but preferably non-reactive under the chosen process conditions. Optionally, the solvent 40 is also immiscible with water. By choosing such solvents, the polymerization tendency of the I'C-I is suppressed and the formation of side reaction by addition of the solvent to the epoxy groups is avoided. Finally, the conversion of the reaction mixture while separating the reactants and the undesired reaction products is facilitated in this way. Particularly suitable solvents are, for example, halogenated hydrocarbons, in particular chlorinated hydrocarbons. The reaction temperature is usually between about 30 and 120 ° C, preferably between 40 and 10 ° C, and in a particularly effective embodiment it is chosen such that the epoxy content of the reaction mixture is reduced by half within 4 to 5 hours.

When these reaction parameters are selected, purification of the crude reaction product is often possible in a very simple manner. The excess of the nucleophilic reaction partner, part of the monoglycidyl compound, as well as the part of the reaction product converted in all three epoxy groups, can often be removed by shaking out the organic phase with water. The beet-reacted TG-I is precipitated by incorporation of the residual reaction mixture into methanol on asantative, Sr finally leaves the crude diglycidyl compound (1: 1 reaction product), which can be purified by column chromatography, for example, by simple fractionation. Siliceous jelly is suitable as a separating agent. -class running fluid can be used, for example, dichloromethane / ethyl acetate or dichloromethane / acetone. The pure preparation and recovery of the two epoxy groups containing 1: 1 reaction product from the mixture of the reagents is here and in the other method outlined below, as a rule, an essential step of the process according to the invention. For the preparation of the sulfoxy compounds from the corresponding mercarto compounds si® Iouben -, 7e3rl aaO, Bend 9 (* 955), 207-21, as well as hakromol.Chen. 16 ^, (1970), 305.

2. A very elegant general process for the preparation of the compounds of the general formula 1 is based on the reaction of the mono-N-substituted cyanuric acids with epihalogenhydrienes. The preparation of mono-IT-substituted cyanuric acids can be carried out according to methods known in the literature. For the relevant literature reference is made, for example, to 77.J. Close, J. Am. Chem. Soc. 22 »0953)? 3617. In addition to older methods which are suitable, a generally applicable method is described here, in which mono-substituted biuret compounds with alkyl-10 carbonates, in particular ethyl carbonate, in the presence of an alkali metal anolate, in particular sodium ethanolate, are converted into mono- substituted cyanuric acids are converted. The substituent introduced in this way generally corresponds to the residue H from the compounds of the general formula 1. In the reaction which follows, both glycidyl groups are introduced. To this end, the mono-substituted cyanuric acids are adjusted in a manner known per se to obtain the appropriate epihaloshydrin compound, for example 20 with epichlorohydrin. This conversion also takes place in an unknown manner. The presence of a small amount of a quaternary ammonium compound as a catalyst can be carried out (see, for example, Houben-7 / eyl, Methods of Organic Chemistry, Vol. 14/2 (1963)). 497, 5-7).

In a modification of this route, the mono-substituted cyanuric acid is not immediately reacted with the epoxy compound. Instead, it is first reacted with allyl halogens corresponding to the glycidyl residue of the compounds of the general formula 1, but instead of the epoxy handle have an ethylenic double bond on which the resulting diallyl-substituted isocyanurates are epoxidized. The epoxidation can be carried out per se with peracids. The reaction of cyanuric acid with allyl halides has also been described in detail in U.S. Pat. No. 3,376,301, the eroxidation of allyl isocyanurates with peracids is described, for example, in Houben-V / eyl aaC, Vol. 6/3 »365 ffhe-40. Thigh, for example, in the presence of a 8005187 11 small amount of var. a quaternary annonization as a catalyst.

The reaction of the monosubstituted cyanuric acids with epihalohydrins or allyl halides 5 is expediently carried out in a temperature range of from about 50 to 150 ° C, preferably from about 70 to about 125 ° C. Allyl halide or epihalcogenhydrogens is used in a molar to cyanuric acid compound ratio of at least 2: 1, but it is also possible to go with a substantial excess of 7 / o, for example up to a molar ratio of 10: 1. ratios in the range of 2 to dnol allyl halide and epihalohydrin per mole cyanuric acid compound can be particularly effective. The preferred allyl halogenes and epihalohydrins, respectively, contain chlorine or optionally bromine as halogen.

The reaction can be carried out in polar aproric solvents which partially dissolve at least one of the reaction partners and are not reactive with the reagents. The particularly delimary solvent is the group of the dialkyl formamides, in particular the dialkyu formamides with a small number of carbon atoms, such as dimethyl formamide. The cyanuric acid compound can be used as such or as a salt. The preferred reaction time is 1 to 1 hour, especially 2 to 5 hours.

The epoxidation of the allyl groups by means of peracids is also preferably carried out in solvents. Polar solvents are also suitable here, for example 50 halogenated hydrocarbons or alcohols. The suitable reaction temperature is usually in the range from 0 to 50 ° C, in particular between about 10 and 30 ° C. The peracid is expediently used in almost equivalent amounts of protein or only in a slight excess. is readily accessible as a commercial product and suitable for carrying out the reaction The reaction time is a range of 2 hours or more, for example up to hours.

Accordingly, the present invention provides, in a further embodiment, the process for preparing N-substituted diglycidyl isocyanuric acid compounds of the general formula 1 wherein H is alkyl, aryl, aralkyl , represents alkaryl or cycloalkyl, which radicals may optionally be of a heterocyclic nature, unsaturated and / or substituted with at least one of the following substituents: halogen, hydroxy, amino, N-substituted amino, mercapto, alkyl mercapto, aryl mercapto, alkylsulfoxy, arylsulfoxy, alkoxy, aroxy, acyloxy and a heterocyclic radical, and wherein glycidyl represents a radical of the general formula II wherein R1 is preferably hydrogen, but may also represent an alkyl radical of 1 to 4 carbon atoms. This process is characterized in that the two glycidyl radicals of the general formula II in M-substitution are introduced into a cyanuric acid with the radical R mono-N-substituted, or a triglycidyl isocyanuric acid with glycidyl radicals of the general formula II in partial conversion with water, alcohols, compounds having a primary or secondary amino group, mercaptans, hydrogen sulphide, carboxylic acids, hydrogen halides or hydrogen, respectively, to produce hydrogen-generating compounds, convert any mercapto compounds formed into corresponding sulfoxy compounds, and the reaction products of the general formula (I) formed from the reaction mixture and as such recover.

In this process, if the two glycidyl radicals of the general formula (II) are introduced into mono-substituted cyanuric acids, this can take place by reacting the cyanuric acid substituted with the radical R with epi-halohydrins, whereby these epihaligen-50-hydrienes correspond to the glycidyl radicals of the general formula II or the mono-substituted cyanuric acid compounds are first reacted with suitable allyl halides, after which the allyl radicals or R-substituted allyl radicals are converted to the glycidyl group by epoxidation with preferably peracids. converted. Due to the properties of the compounds of the general formula I, the radicals R and glycidyl and the reagents for forming these radicals, all directions given above apply.

The compounds of the general formula 1 in purified and bulk form are new compounds.

They fall as such and in particular in the isolated form suitable for use as a medicine within the scope of the present invention. Also for this aspect of the invention the above general directions apply to the definition of the compounds of the general formula 1 with their residues E and glycidyl. The Budnowski literature site, Angewandte Chemie 80 (1968), 851, formulates a reaction product as an intermediate step of the reaction of a large excess of epichlorohydrin with zyanic acid as an intermediate step. epoxy groups in h-substitution contain a 2-hydroxy-3-chloropropyl substituent. It is stated that this tussen product was shown thin-layer chromatographically. The isolation of this compound 15 as such in the mass is not described, moreover, the compound according to this literature reference is formed by a route which has nothing in common with the method outlined above.

Finally, the object of the invention is also the use of the compounds of general formula 1 for the therapy of the malignant forms of neoplasms. Separate administrations of the compounds in an amount of 1 to 200 mg / kg may be effective. Sr, individual, certain compounds of the general formula 1 or mixtures thereof can be used. Also their application mixed with IGI is within the scope of the invention,

The compounds of the general formula I used according to the invention exist in different stereoisomers. In principle, all these different shapes are suitable for the purposes of the invention. They can be mixed or used in the form of certain isolated isomers. .

For use as cancerostatics, the active products must be applied by suitable carriers. Suitable for this purpose are the usual auxiliaries or carriers for pharmacological preparations. In the present case, the use of aqueous systems, optionally together with compatible glycol ethers, such as 4-0 glycol noncethyl ether or butylene glycol methylPher or pro-.

800 518? Pylene glycol methyl ether has been found to be suitable, especially when the active agent is to be administered parenterally. When administered orally, the pharmaceutically customary excipients or carriers are useful, provided they have suitable compatibility with the glycidyl compounds.

In the animal experiment, the use of freshly prepared aqueous solutions administered intraperitoneally or intravenously has been found to be effective.

The compounds used according to the invention are effective against various forms of leukemia, as well as malignant neoplasms, such as lung carcinoma, intestinal carcinoma, melanomas, ependymoblastoma and sarcoma. It has been found that in some cases a markedly better effect can be observed in comparison with cyclophosphamide and fluorouracil.

A combination therapy together with other cytostatics, such as derivatives of the nitrogen solution or also fluorouracil is possible.

Very generally, it applies to the compounds of the general formula 1 with their residue H used in the context of the invention, that this residue has at least under normal conditions no or no substantial reactivity with the epoxy groups of the glycidyl substituent (() on the nngsy-25 system of the general formula 1 shows and will show.

In this way it is ensured that the active substances used according to the invention have a long shelf life and no undesired conversion takes place while the epoxy groups are destroyed. This rule should in particular also be taken into account when selecting any substituents present in the remainder R.

Examples of the residue R of the compounds of the general formula 1 with cyrostatic activity used according to the invention are the following:

Methyl, ethyl, propyl, butyl, pentyl, hexyl, the corresponding isomeric radicals such as isopropyl, isobutyl, tert-butyl, isopentyl, suitable unsaturated, especially ethylenically unsaturated radicals such as vinyl, allyl, 40 butenyl, phenyl, benzyl, xylyl, trimethylphenyl, isopropyl-8005187, phenyl, naphthyl, cyclopentyl, cyclohexyl, the corresponding cycloaliphatic radicals substituted with 1 to 3 alkyl radicals or alkenyl radicals, the alkyl substituents or aikenyl substituents, preferably 1 to 4 carbon atoms, 2,3-dihydroxy 2-hydroxy-3-diethylaminopropyl, 2-hydroxy-3-dinethylamino-propyl, 2-hydroxy-3- (dihydroxyethylamino) -propyl, 2-hydroxy-3-morpholinopropyl, 2-hydroxy-3-snoxypropyl, 2-hydroxy-3-methoxypropyl, 2-hydroxy-3-ethoxypropyl, 2-hydroxy-3-pro-10-poxypropyl, 2-hydroxy-3-acetoxypropyl, 2-hydroxy-3-propyloxypropyl, 2-hydroxy-3 -butyloxypropyl, 2-hydroxy-3- (3-carboxypropyloxy) -propyl, 3-hydroxy-2-acetoxypropyl, 3-hydro xy-2-propyloxypropyl, 3-hydroxy-2-butyloxypropyl, 3-hydroxy-2- (3-carboxypropyloxy) -propyl, 2-hydroxy-3-chloro-15-propyl and 2-hydroxy-3-bromopropyl.

Other examples of the possibilities for R within the scope of the invention are the following radicals: generally haloalkyl, hydroxyalkylthiopropyl, 2-hydroxy-3-methylaminopropyl, 2-hydroxy-3-sthylaminopropyl, 2-hydroxy -3-di (β-chiporethyl) aminopropyl, 2-hydroxy-. 3-renzyloxypropyl and 2-hydroxy-3-hydroxypropyioxypropyl. Other options for the radical R are 2-hydroxy-3-methylthiopropyl, 2-hydroxy-3-butylthipropyl, 2-hydroxy-3-phenylthiopropyl, 2-hydroxy-3- (benzoxazoi-2'-ylthio ) -propyl, 2-hydroxy-3-acetothiopropyl, 2-hydroxy-3-octylthiopropyl, 2-hydroxy ^ 3 (2 (.3'-dihydroxypropylthio) -propyl, 2-hydroxy-3 (benzimidazo-2'-ylthio) propyl, 2-hydroxy-3 (benzthiazol-2'-ylthio) propyl.

Reagents for the conversion of a glycidyl group. in the triglycidyl isocyanurate to form a substituted residue R within the meaning of the invention, very generally alkanols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec.butanol, tart, butanol, 1- pentanol, 2-pentanol, 3-pentanol, 2-methyl-1-butanol, 3-methyl-1-butand, 2-ethyl-2-butanol, 3-methyl-2-butanol, 2,2-dimethyl-1-propanol 1-hexanol, 2-ethyl-1-butanol, 4-methyl-1-pentanol, 4-methyl-2-pentanol, 2-methyl-1-pentonol. Examples of unsaturated alcohols are 2-buten-1-ol, 2-propyn-1-ol, allyl alcohol, crotyl-40 alcohol, 3-buten-2-ol, 2-buten-1-ol, and 3 -butyn-2-ol.

e η Λ K i Q 1

Examples of polyhydric alcohols are ethylene glycol, propanediol-1.2, propanediol-1,3> butanediol-1,4, butanediol-1,2, butanediol-2,3-butanediol-1,35 2-butenediol-1,4-, 2-butyne-1,4 - diol, 1,5-pentanediol, 2-methyl-1,4-butanediol, 2,2-dimethyl-1,3-pi-opiol, hexanediol, 2,5-dimethyl-5-hexyn-2,5-diol, glycerol, 1,2.4-- butanedriol, 2-hydroxyethyl-2-ethylpropanediol, 2-methyl-2-hydroxymethyl-1,3-propanediol, pentaerythritol. Examples of thiols in this connection are methanethiol, ethanediol, 1-propanethiol, 2-propanethiol, 2-methyl-2-propanethiol, 2-butanethiol, 2-methyl-1-propanethiol, 1-butanethiol, 1-pentanethiol, 1- hexanethiol, as well as 1,2-ethanethiol, 2,2-propanethiol, benzenethiol, p-benzenedithiol, pyridine-2-thiol and thiophene-2-thiol. 3rd sulfoxide compounds to be obtained from such nercaptor residues fall within the scope of the invention. Examples of carboxylic acids are in particular acetic acid, propionic acid, n-butyric acid, n-valeric acid, capric acid, oenanthic acid, isobutyric acid, 3-methylbutanoic acid, 2,2-dinethylpropanoic acid, 2-methylbutanoic acid, 2-ethylbutanoic acid, 2-ethylhexanoic acid. Unsaturated acids are, for example, propenoic acid, 2-methylpropenoic acid, 3-esthylpropenoic acid, 2,3-dimethylpropenoic acid, hexadienoic acid, propiolic acid. Examples of substituted acids are 2-chloropropanoic acid, 3-chloropropanoic acid, 2,2-dichloropropanoic acid, 2,3-dichlocr-23-propanoic acid, 3 * 3-dichloropropanoic acid, 2,2.3.3 * 3-PeK-tachloropropanoic acid, 2-chlorobutanoic acid, 3-chlorobutyric acid, -4 · -chlorobutanoic acid, 2-chloro-2-methylpropanoic acid, 3-chloro-2-methylpropanoic acid, 2,3-dichlorobutanoic acid, 2,2,3-trichlorobutanoic acid, 2-chloropentanoic acid, 3-chloropentanoic acid, 30 4-chloropentanoic acid, 5 -chloropentanoic acid, 2-chloro-2-methyl-butanoic acid, 2-chloro-3-methylbutanoic acid, 3-chloro-2,2-dimethylpropanoic acid. Examples of aromatic acids are benzoic acid, phthalic acid, isophthalic acid, terephthalic acid and the corresponding acids substituted with methyl or ethyl residues. Other examples of substituted acids are glycolic acid, hydroxybutyric acid (α, β and X-vcrm respectively), hydroxybenzoic acid with the hydroxyl group at the o, n or p position, the hydroxybenzic acids with the hydroxyl groups at the

X h__ O X— O X n O ^ _ ~ r \ *] pp-f-q • V.'h-rrP

4-0 sour. Phenolic compounds include, for example, 8005187 17 marking phenol, cc and β-naphthol, cresols, xylnols, chlorophenols, chlorocresols, chloroxylenols, methylenols with optionally more than one methyl group, for example 2.3 · 4-trimethylphenol, ethylphenols, propylphenols ,.

Butylphenols and the like. Examples for the conversion of the glycidyl groups with amines are: methylamine, dimethylamine, ethylanine, diethylamine, n-propyl amine, di-n-propylamine, isopropyl amine, di-iso-propylamine, n-butyl amine, di-n-butyl, amine, sec-butylamine, di-sec-butylamine, is0-isobutylamine, di-iso-butylamine, tert-butylamine, n-amyl-amine, di-n-anyl amine, sec.n-amylamine, iso-amylamine, di-iso-amylamine, allylamine, di-allylamine, cyclohexylamine, H-methylcyclohexylamine, dicyclohexylamine, cyclooctylamine.

Examples of cyclic compounds with amino groups 45 are piperidine, hexamethyleneimine, morpholine, aniline, cc and β-naphthylamine, respectively.

The percentages given in the examples below refer to percentages by weight, unless stated otherwise.

Example I

Preparation of diglyciayl-2,5-dihydroxynronyliocyanurate 10 C g of driglycidyl isocyanurate are stirred in 1000 ml of water with a pH of 7 to 70 ° C for 3 hours. The undissolved residual starting product is filtered after cooling of the solution and the solution is generated under reduced pressure with an oil pump, gently evaporated to dryness. The mixture contains 9.1% by weight epoxy oxygen and consists essentially of a mixture of diglycidyi-2,3-dihydroxypropyl isocyanurate and glycidyl di (2,3-dihydro-30. Xypropyl) iso cyanurate.

The mixture is fractionated by column chromatography.

The column with a diameter of 3.cm is filled with 170 g of silica gel from 0.063 to 0.2 mm. As the eluent, a mixture of dichloromethane / ethyl acetate 3 + 2 + 5% metha-33 wool is used.

At an initial weight of 38 g, 18 fractions of 100 ml each are isolated. Fractions 10 to 18 gave 21 g of the desired compound.

% EpO: 10.3 (theory 10.1), colorless syrup.

40 Refractive index n ^ = 1.3093 8005187

Mass spectrum and H-ITMS. support the structure.

Example II

Preparation of diglycidyl-2-hydroxy-3-chloropropyl isocyanurate.

5 moles of cyanuric acid, 60 moles of epichlorohydrin and 0.02 moles of tetraethylammonium bromide are refluxed for 3 hours. The reaction is terminated in 1/2 to 3/4 h after dissolution of the cyanuric acid. The excess epichlorohydrin is generated under reduced pressure with the water jet pump. The dichlorohydroxypropane is then distilled under reduced pressure generated with an oil pump (0.013 kPa) on the oil bath (70 to 100 ° C). This distillation must be carried out very carefully, because even small amounts of non-removed dichloro-hydroxypropane decrease the yield.

Triglycidyl isocyanurate crystallizes from the remaining pale yellow resin after addition of methanol overnight in the refrigerator; yield 35 to 40%.

The methanol phase is concentrated at 50 ° C using the oil pump and consists of a mixture of about 70% di-glycidyl-2-hydroxy-3-chloropropylisocyanurate and 20% glycidyl-di (2-hydroxy-3-chloropropyl / isocyanurate.

Thin layer chromatogram on Kerck F 60 silica gel (eluent: dichloromethane: ethyl acetate 6: 4).

RF values di-glycidyl compound 0.40 mono-glycidyl compound 0.27 Analysis values: 8.1% BpO (calculated: 8.2%) 12.1% Cl (calculated: 12.5 $).

The individual components can be neatly prepared by column chromatography.

The yield of diglycidyl compound is about 30%, pale yellow, very viscous liquid, epoxy oxygen 9.3% (calculated 9 * 6%), chlorine content 10.95% (calculated 10.65%)

Example III

Preparation of Diglycidyl Methyl Isocyanurate 1 mole Kethyl cyanuric acid (W.J. Close, Journal of the American Chemical Society, 21 (1953) 3618) is refluxed with 90 moles of epichlorohydrin and 0.1 moles of tetramethylanmorium chloride for 40 hours.

8005187 19

The reaction product is intensively refluxed at 40 to 50 ° C under reduced pressure. 3 niol HaOH (4-0% in water) are slowly added dropwise under intensive stirring and 5 at the same time the water is continuously azeotropically distilled. The mixture is stirred for an additional 30 minutes, the table salt is filtered off and concentrated to dryness under reduced pressure.

The resulting pale yellow resin has an epoxy content of 11.6% (calculated 12.5%). The structure became. confirmed by the mass-10 spectrum.

Example IY.

Preparation: of diglycidyl- (S-hydroxyl-diethyl-aminorovol) isocvanurate, 10 g of α-triglycidyl isocyanurate and 12 g of diethylamine 15 are dissolved in 250 ml of absolute toluene and heated to 60 ° G for 6 hours with exclusion of moisture. The toluene is distilled under reduced pressure and the resinous residue is mixed with 50 ml of methanol. Overnight, the unconverted IGI (about 5 g) crystallizes almost completely. The mother liquor was evaporated and consists of a mixture of the aforementioned compounds, the glycidyl compound clearly predominating. The epoxy content of the mixture is 6.3 c / o. The thin layer chromatogram (silica gel, dichloromethane: ethyl acetate: dimethylamine 25 55 "4-5" 2) shows two spots after carbonization with sulfuric acid. EE = 0.5 diglycidyl compound, H? = 0.2 monoglycyl compound, intensity ratio 5: 1.

The crude product is fractionated via a silica gel column (length 50 cm, diameter 5 cm). As the eluent-50 agent, dichloromethane: ethyl acetate 3: 2 + 15% methanol is used. -

The mass spectrum and the H-MiE spectrum support the structure of the isolated diglycidyl (2-hydroxy-3-diethylamino-propyl) isocyanurate.

35 Example V

Preparation of those: lycid7 / 1- (2-h7 / droxv-5-H-morpholinooroo7 / l) isocvanurate 29.7 g (0.1 mol) α-triglycidyl isocyanurate and 10 g (0.115 mol) morpholine 4-0 are analogous to example IV.

sea weight of the reaction product: 32 g, DG (silica gel, eluent dichloromethane: ethyl acetate 3 '2)% EpQ: 5.8 diglycidyl compound HP 0.5 monoglycidyl compound RE 0.15.

The crude product is fractionated via a silica gel column (length 50 cm, diameter 5 cm).

Eluent: dichloromethane: ethyl acetate 3 * 2 + 15% methanol.

reeral low weight of the diglycidyl compound: 19 g very light-10 yellow syrup% EpO: 8.5 (theory 8.6) Ί

The mass spectrum and the H-3SKR spectrum support the structure.

Example VI

Preparation of diglycidyl-Γ 2-h: njroxv-3- (2-hydroxyethyl-thio) -prouyl-1-isocyanurate 29.7 g (0.1 mol) cc-glycidyl isocyanurate and 8.0 g (0.1 mol) mercaptoethanol and 1.5 nil triethyiasin in 500 ml dichloromethane are kept under reflux for 3 hours. The mixture is then shaken with 3x 60 ml of water, dried over sodium sulphate and then concentrated.

The product is taken up in 200 ml of methanol and the precipitated TGI is filtered off. The methanol phase is concentrated to give 16 g of a mixture of the mono- and the diglycidyl compound.

% SpO: 6.1

The reaction mixture is separated by column chromatography. The 4 cm diameter column is filled with 250 g of silica gel 60. As the eluent, dichloromethane: ethyl acetate: methanol is used 3: 2: 1.

Diglycidyl compound weight: 10.5 g% EpO: 8.2 (theory 8.5) 20

Refractive index n ^ = 1.5207 35 Example VII

Preparation of diglycidyl allyl isocyanurate 20 g (0.08 mol) triallyl isocyanurate, 30 g (0.176 mol) 3-chloroperoxybenzoic acid in 600 ml dichloromethane are left for 100 hours at 5 ° C and 24 hours at ambient temperature. 40 The solution is then mixed with a sodium carbonate solution 8005187 21. . β 3χ washed out and the dichloromethane phase concentrated. Impure weight: 26 g of oily liquid.

The crude product is taken up in methanol and precipitated. The first precipitate contains triglycidyl isocyanurate with a melting point of 70 to 115 ° C. The second precipitate contained 6.4 g of a reaction product with a melting point of 50 to 55 ° C,% SpO: 9.0 (theory 11.4), iodine value: 14-3 (theory 90).

This crude product is fractionated on a silica gel column (diameter 5 cm, length 4-0 cm), which is filled with silica gel 60, with dichloromethane: ethyl acetate 3: 2 as eluent and recrystallized from methanol.

..... Weight of the diglycidyl compound: 2.4 g, melting point 57

15 to 60 ° C

iodine value: 102 (theory 9θ) epoxy content: 11.1% (theory 11.4.%).

Example VIII

Preparation; of diglr / cidyl- (prey GnrtLoxy ^ hyHroxy-OrQoyl) - 20 isoc / anurate 20 g (0.067 mol) a-Iriglycidyl isocyanurate and 50 g (0.67 mol) propionic acid are added in 300 ml of toluene for 4.5 hours with addition of 10 g of a molecular sieve of 3® kept at reflux. Then it is filtered and concentrated.

Impure product weight: 23.5 g.

The mixture is taken up in 150 ml of methanol, the precipitated TGI is filtered off and the methanol phase is concentrated. After fractionation on a silica gel column, 17.2 g of a colorless syrup remain.

° / o. EpO: 8.1 (theory 8.2).

The mass and E-MK spectrum support the structure.

Example IX

55 Preparation of diglycidyl- (2-hydroxy-5-yl-ro-DoxyOrouyl) isocyanurate 29.7 g (0.1 mol) of α-triglycidyl isocyanurate and 30 g (0.5 mol) of n-propanol in 500 ml of toluene stirred at reflux for 6 hours. The solution is then concentrated and taken up in 200 ml of methanol. The TGI precipitated TGI is suctioned off and the methanol phase concentrated again.

Reaction product weight: 15 g of oily syrup.

The mixture is fractionated by column chromatography. The column has a diameter of 5 cm, a length of 50 cm and is filled with 250 g of silica gel 60. As the eluent, dichloromethane: ethyl acetate 3 · 2 is used. Diglycidyl compound weight: 12 g% EpO: 8.9 (theory 9.0).

In the thin layer chromatogram, the compound shows an RF value of 0.35 (dichloromethane: ethyl acetate 3: 2). Mass spectrum and H-EMR confirm the structure.

Example X.

Preparation of Diglycidyl HydroxyOlisocranurate 15,94 g (0.02 mol) of α-triglycidyl isocyanurate are dissolved in 200 ml of ethanol / water (7: 3). Then 0.76 g (0.02 mol) of sodium borohydride are added and the ambient temperature is stirred for 5 hours. The cloudy solution is acidified with dilute hydrochloric acid, filtered and then extracted 3x with 200 ml of dichloromethane each time, dried over magnesium sulfate and concentrated again.

Weight of the crude product: 8 g% EpO: 8.5 (theory 10.7).

Set of crude reaction mixture is fractionated by means of a silica gel column. The column has a diameter of 5 cm and a length of 4-5 cm and is filled with silica gel 60. As the eluent, dichloromethane: ethyl acetate: methanol is used 3: 2: 1.

30 Weight of the diglycidyl compound: 3.7 g% EpO: 10.6 (theory 10.7).

The compound has an RF value of 0.4-5 (dichloromethane: ethyl acetate: methanol 3: 2: 1) in the thin layer chromatography on silica gel.

Example XI

Preparation of diglycidyl-2-hydroxv-3 (21,3'-dihydroxyoropylthio) -Orooyl isocyanurate 10 g (0.034 mol) Iriglycidyl isocyanurate, 3.3 g (0.034 mol) 1,2-dihydroxy-3-mercaptopropane and 0.1 g of triethylamine 40 were dissolved in 200 ml of methanol, respectively suspended, and stirred at 40 ° C for 3 * 5 hours. After careful distillation of the solvent, 13 g of the product mixture remain, which is separated by column chromatography with silica gel 60 (Burma Merck) and ethyl acetate / methanol 80/20 as eluent. Yield of mono-addition product 1.6 g (11.6%)% epoxy oxygen: 7.92 (theory 7.89)

Example XII.

Preparation of dis: lycidyl-2-hydroxy-3-n-octylthioororyl isocyanurate 10 g (0.034 mol) triglycidyl isocyanurate, 5 g (0.034 mol) n-octyl mercaptan. and 0.1 g of triethyl prophine were dissolved in 200 ml of methanol, respectively suspended and stirred at 40 ° C for 3.5 hours. After distillation of the solvent, 16.1 g of the product mixture are left, which is separated by eluent by column-13 separation with silica gel 60 (Burma Merck) and ethyl acetate: dichloromethane: n-hexane. 3 g, 1.4 g of an 83% product (yield 7.7% of theory) with 6.21% epoxy oxygen were isolated. The structure corresponds to the above-mentioned mono-addition product.

Example XIII

Preparation of diglycid-1-2-hydroxy-5 (benzthiazol-21-yl-thio) -oroul / lisocyanurate 10 g (0.054 mol) Triglycidyl isocyanurate, 5.7 g (0.034 mol) 2-mercaptobenzthiazole and 0.1 g triethylamine was dissolved in 200 ml of methanol respectively suspended and stirred at 40 ° C for 2.5 hours. After distillation of the solvent, 12.7 g of a pale yellow solid product remained, which was column chromatographed with silica gel 60 (Burma Merck) and ethyl acetate: dichloromethane 60:40. Sr, 2.0 g of a 92% mono-addition product of the aforementioned structure were isolated (yield 11.4% of theory), 6.31% epoxy acid. The compound is solid and colorless.

Example XIV

Preparation of. diglycidyl-2-hydroxy-5 (benzimidazol-2'-yl-thio) -orooislisocanurate 10 g (0.034 mol) 'triglycidyl isocyanurate, 5.1 g (0.034 mol) 2-mercaptohenzinidazole and 0.1 g of triethylamine 40 were taken in 200 ml of methanol dissolved respectively suspended in suspension and stirred at 40 ° C for 2 hours. After distillation of the solvent, 13.0 g of a solid product remained, which was column chromatographed with silica gel 60 (Firma Merck) and ethyl acetate. Fr 1.8 g of a 89% product were obtained, which is solid and colorless and has an epoxy oxygen value of 5.35. Yield 10.5 '1 ° of the theory.

Example XV

The following tests were performed according to test-10 regulations of the National Cancer Institute Bethesda, Maryland 200014, published in "Cancer Chemotherapy Reports" part 3? September 1972, Vol. 3 »No. 2. The compounds of the invention were used as the active product. The products were freshly prepared as aqueous 1 percent injection solutions immediately before use.

In mice, according to Protokol 1200 (p. 9 l.c.) r, the tumor type P 388 (leukemia) was injected i.p. just placed 10 ° cells / mouse. The mean survival of the thus pretreated animals was determined in a control group (C).

In test groups of animals pretreated in the same manner, the active compounds according to the invention are administered in 3 doses. In the different test series, slightly varying amounts of the active ingredient in question are used. The average lifespan of the test group in question is determined (I). Comparison with the mean survival of the test group thus treated relative to the untreated control group gives the degree of elongation T / C, determined in 30%. This degree of T / C extension is a measure of the efficacy of the compound used in the test. In the following table the T / C values are summarized depending on the administered concentration of the active substance concerned.

25. = label

Example Concentration Working T / C (%) Recurrence Solid / Administration _______ III 10C 258 _______50 _ 20 ^ __ VII 100 248 _5C 250 ______ V 200 255 305 100 196 217 50 145 166 _25 _ 161 "X IOC 250 50 18? 226 25 174 _ 12.5 _; _ 167 I 100 300 50 203 300 25 197 _____12_j_5_ 174 VIII 100 255 269 50 184 216 2 ~ 191 Λ OC ΛζΖ.0 ____: _! -> _ IX 100 213. 271 50 184 262 or * ✓} ^ 1 * - 1 J _- _ '^ s „VI 100 265 271 50 262 284 25 298 __ 12.5 192 IV 1C0 154 __50 _: _ 16 ^ _ II 100 212 173 _ 50 ITS_ 455 XII 200 143 XI 200 190 100 151 __50 155______ r = -CHp-CH-CHp- :: (c ^ oh) 2 0H 200 167 100 140 80 0 5 1 8 7

Claims (10)

2. Preparation according to claim 1, with the knowledge that one or more compounds of the general formula 1 are present, in which the residue R does not amount to less than 1p carbon atoms, preferably not more than 12 carbon atoms and in particular not contains more than 8 carbon atoms. Preparation according to claims 1 and 2, characterized in that the preparation contains one or more compounds of the general formula 1, wherein R is an optional Se ~. substituted alkyl radical with at most 1C carbon atoms, preferably with at most δ carbon atoms and in particular with at most 3 carbon atoms. 4- A composition according to claims 1 to 3, characterized in that the composition contains one or more compounds of the formula 1, wherein R represents an alkyl moiety substituted with at least one hydroxyl group. Preparation according to claims 1 to 4, characterized in that in the compounds of formula I the radical R is a hydroxyalkyl radical containing at least one of the following substituents: hydroxy, halogen, amino, substituted amino, alkyl-nerapto aryl mercapto, alkyl sulfoxy, aryl sulfoxy, alkoxy, aroxy, acyloxy. 6. A composition according to claims 1 to 5, characterized in that the nerarate contains one or more of the compounds of the formula 1, the radical R 40 being substituted or monohydroxylated alkyl with 1 to 8005187-27 material atoms or disubstituted alkyl net. 3 to 7 carbon atoms such as dihydroxyalkyl, halohydroxyalkyl, IT-substituted quinohydroxyalkyl, alkoxyhydroxyalkyl, alkyl mercaptohydroxyalkyl, alkyl sulfoxyhydroxyalkyl and acyloxy-3 hydroxyalkyl. Preparation according to claims 1 to 6, with the knowledge that the preparation contains one or more compounds of the formula 1, wherein 3 is a disubstituted alkyl radical with 3 carbon atoms, which is the hydroxy group at 2- or 3-513 -3 ^ 13 and. the other substituent at the other of the two positions mentioned in the alkyl group having 3 carbon atoms. 8. A composition according to claims 1 to 7, characterized in that the composition contains mixtures of more compounds of the general formula 1 and / or mixtures of these compounds with triglycidyl isocyanurate (T'GI). 9. Preparation according to claims 1 to 8, characterized in that the preparation as compounds of the general formula 1 contains conversion products of 2Gj. mer 20 contains hydrogen halide, water, compounds having a primary and / or secondary amino group, carboxylic acids, alcohols, phenols and / or aliphatic and / or aromatic thiols, respectively, hydrogen- or hydrogen-yielding compounds. 10. A composition according to claims 1 to 8, characterized in that the composition comprises reaction products of mono-N-substituted cyanuric acids with epinic hydrenes or just allyl halogenia and subsequent epoxides of the double bonds of the a-n / lg-oe .. b ^ 30 barrel. 11. Preparation according to claims 1 not 10, m e t. it is known to the person skilled in the art that the preparation contains compounds of the general formula 1 mixed with customary zero-to-L-phen and / or carriers. 35. 12. C-lycidyl isocyanuric acid compounds take formula 1, wherein 3 is alkyl, aryl, aralkyl, alkaryl or cycloalkyl, which also contains residues of heterocyclic unsaturated and / or with at least n vSxx substituents substituted may be 4-0 amino, r-substituted amino, mercaprc, 8005187 aryl mercapto, alkyl sulfoxy, aryl sulfoxy, alkoxy, aroxy, acyloxy and a heterocyclic moiety, and wherein glycidyl represents a general formula 2 wherein hydrogen or an alkyl radical of 1 to d carbon atoms. 13. Process for the preparation of isocyanuric acid compounds, characterized in that compounds of the general formula 1, in which the symbols have the meanings stated in claim 1, are prepared in a manner known per se. 14. A process for the preparation of isocyanuric acid compounds, characterized in that compounds of the general formula 1, in which the symbols have the meanings stated in claim 1, are prepared in that a mono-R-substituted cyanuric acid with the residue R The two glycidyl radicals of the general formula 2 in R-substitution by reacting the cyanuric acid compound with epihalohydrins and with allyl halides and therefore subsequent epidoxidation to glycidyl residue with the P Ί / ** \ 1] O η wtTA ΛΠ · 1 · Γ \ - f1 ^ ^ Vv Ή rrA η -15 -ί ^ / -ν / Λ π ι 1 _ d_Lgj _ vj — iu. J-w £ 1 v u Oi C? t3__ t ^ ^ J ^ 1 vlJ ^ ü m uU_ ”20 compound with glycidyl residues of the general formula 2 on a partial conversion with water, alcohols, compounds with a primary and / or secondary amino stirrer, mereaptanes, sulfur ester, carbonic acids, hydrogen calide cf hydrogen or hydrogen-providing compounds 25, if desired, converting formed mercapto compounds to corresponding sulfoxy compounds, the formed prvpf; rl '7 TTl' ^ 'h ^ ^ el joTione -Pr1 1ρτη 7 ·? 1 p Ί ir! 1 ^ 4- J- O - C ^ 1> J di. \ J-fi. J O iJ. ± ii, vj \ ^. V ^ iu - <mJ. «W \ J _ ui lA -J. C1 l U.-i. vj • sx u _ _ »m ^ 'O CT Q ~ Ί ^ 41 fi-p p 1] c ^ p, ^ p 10 4 ~ rrr-? p 4- iil -w> Ijl q W V j- '-'S ™ O O -.U. J_ vj »v_ <'" - / ui νΛ.LO \ J <w4. W1.i_ Q> J aL · JJ VJ · 8005187 # sje # # x R yV Ί KL Glycicb / l ^ ^ GlycidyL 0 2. ΐ - CH2 -C - CH2-3 NHRa or NR2 R3 8005187